Meningiomas

Shikher ShresthaNINAS

History

Harvey Cushing, 1922; series of 85 meningeal tumors in Cavendish lecture

Coined the term “meningioma”

Louise Eisenhardt, created definitive monograph years later

He believed that all meningeal tumors arose from the arachnoidal cap cells that are particularly abundant in the arachnoid granulations

Common brain tumor

Wide variety of clinical behaviour – benign to aggressive

Unknown etiology; but implicated to

previous radiation therapymonosomy or partial loss of

chromosome 22trauma

Epidemiology

15-20% of all primary intracranial tumors

Incidence in routine screening: 1 in 100 population

Incidence increases with advancing age

Predominantly affect women: overall male:female ratio of 1:2.5

Difference is more in intraspinal meningioma 1:10

Meningeal tumors are rare in children: more aggressive if present then

0.4 to 4.1% of all childhood brain tumors

And constitute only 1.5 to 1.8% of all meningiomas

Pediatric meningiomas are more common in males M:F::1.2-1.9:1

Symptomatic meningioma 2/1,00,000 and asymptomatic 5.7/100,000 with overall incidence of 7.7/100,000 in general population

May be multiple in 8% cases

Occasionally forms a diffuse sheet of tumor – meningioma en plaque

Ectopic meningiomas: may arise within the bone of the skull (primary intraosseous meningiomas) and subcutaneous tissue with no attachment to skull

~25% of adolescent meningiomas are associated with NF1

Commonest type: parasagittal followed by convexity and tuberculum sellae

General Clinical Presentation

Asymptomatic to wide variety of symptoms

S&S related to compression of adjacent structures

Prerolandic cortex: motor seizures and contralateral limb weakness

Postrolandic cortex: sensory deficits and Jacksonian seizure

Broca’s or Wernicke’s area: speech disturbance

Large frontobasal tumors: visual field impairment or behavioral disorder

Olfactory groove: Anosmia

Intraventricular: Obstructive hydrocephalus

Spinal: Limb weakness, numbness or local pain

Inner sphenoidal wing: visual impairment due to optic nerve compression, central scotoma; Foster Kennedy syndrome

Cavernous sinus/ superior orbital fissure: ptosis and impaired eye movement (III, IV, VI) or facial pain and anesthesia (V1 nerve damage); Proptosis: venous obstruction or tumor extension to orbit

Imaging

Contrast enhanced MRI with addition of arterial and venous sequences

CT : bony anatomy

3D MRI or CT scans: useful for surgical planning

Plain Radiographs:HyperostosisIrregular cortexTumor CalcificationsEnlargement of Vascular grooves (middle meningeal artery)

Computed Tomography

Well circumscribed extra-axial lesionhyperdense (70-75%)isodense (25%)hypodense (1-5%) to parenchyma

Calcifications ranging from microscopic psammoma bodies to dense sclerosis are found in 25% patients

Necrosis, cysts and hemorrhage seen in 8-23%

Bright enhancement with contrast agent

Magnetic Resonance Imaging

T1 weighted isointense to moderately hypointense to gray matter lesionscalcification and highly fibrous areas are hypointenseFLAIR (Fluid Attenuated Inversion Recovery): hyperintense signal in the adjacent parenchyma

T2 weighted – wide range of possible signal intensitiesisointense or mildly hyperintensehypointensity if calcified or highly fibroussurrounding edema as hyperintense signalArterial feeders seen as arborizing flow voids (hypointense)Pial blood vessels as surface flow voids between tumor and parenchymacalcifications and microhemorrhage as low signal in T2 GRE gradient

echo

T1 contrast enhancementheterogenous clearly define hyperintensive image

dural tail in 35 to 80% but is not specific

MRA and MRVnon invasive option to demonstrate tumor blood

supply, vascularization, drainage veins, and sinus compromise

Functional MRIbased on increased brain hemodynamics in response to cortical

neuronal activity due to certain stimulus performed during imaging

helpful in surgical planning for localization of motor, sensory, and language regions

Diffusion may differentiate benign from atypical or malignant meningiomas

Perfusion reveals differentials in relative cerebral blood volume (distinguished meningioma from cerebral metastasis)

Spectroscopy:

high choline peak, low or absent N-acetylaspartate (NAA) and creatinine

variable amounts of lactate

some of them present with high alanine and glutamate/glutamine level

Angiography- classic pattern “comes early, stays late”

Invasive study

Demonstrate primary blood supply derived from dural arteries (branches of external carotid artery)

Feeding vessels could be bilateral, especially in falcine or parasagittal meningiomas

Degree of vascularization and major draining veins are also seen

Venous phase important to evaluate sinus involvement and presence of AV shunting

Allows possiblity to perform preoperative selective embolization, usually several days before surgery

Positron Emission Tomography

Role not clear

Benign variant: isometabolism with 18F- Fluorodeoxyglucose (FDG) markers

Atypical/anaplastic: hypermetabolism

FDG uptake could be a predictive factor in tumor recurrence

Single-Photon Emission Computed Tomography Scintigraphy

Meningiomas have many somatostatin receptors (SSr)

SPECT can image SSr positive tumors in vivo

Octreotide (somatostatin analog) has high binding affinity to SSr subtype 2 with longer plasma half life than native somatostatin

Octreotide is a better SSr imaging agent than somatostatin

Pathology

Hormone receptors

growth related to hormonal status due to presence of estrogen and progesterone receptors

The tumor may become clinically evident during pregnancy or luteal phase of the menstrual cycle

progesterone receptors expression related to favorable behavior

estrogen receptor correlates with aggressive behavior, progression, and recurrence after complete surgical resection

Therapies targeting hormonal status have not been particularly successful

Immunohistochemistry:

Useful in distinguishing certain tumor types from them

Focal positive staining with epithelial membrane antigen (EMA) – absent in WHO grade II and III variants

All subtypes exhibit vimentin diffuse positivity, but not pathognomonic

Variable positivity staining with S-100 and cytokeratin markers

Secretory variant of meningioma has positive staining to CEA

Schwannomas vs Meningiomas in immunohistochemisty

Immunoreactivity for S-100 protein is focal and low in meningiomas and strong in schwannomas

EMA is commonly absent in schwannomas

Classification of Meningiomas

Grade I:

Defined as absence of Grade II and III

Subtypes: meningothelial, fibroblastic, transitional, angiomatous, microcystic, secretory, lymphoplasmocyte-rich, metaplastic and psammomatous(9 subtypes)

No prognostic significance among various subtypes

Grade II (atypical meningiomas)

Presence of 4 or more mitotic cells per 10 high-power fields or

Three or more of the following features:

increased cellularityhigh nuclear/cytoplasmic ratiogeographic necrosisprominent nucleolisheet like growthbrain invasion

2 morphological subtypes of Grade II

Clear Cell:Lobulated or sheet like proliferations of polygonal cells with clear, abundant glycogen cytoplasm (periodic acid-Schiff positive)

Higher incidence of recurrence

Young patients

Spinal and cerebellopontine locations

Chordoid type:

Presence of cords of eosinophilic, epithelial like, and vacuolated cells

Prominent myxoid background, like in chordoma

Chronic inflammatory cell pattern, dysgammaglobulinemia and microcytic anemia (Castleman’s disease)

High rate of recurrence after subtotal resection

Grade III (anaplastic)

Presence of 20 or more mitoses per 10 high-power field

Malignant cytological characteristics resembling carcinoma, sarcoma, melanoma

Rhabdoid:Rhabdoid like cells with prominent eosinophilic cytoplasm, prominent nucleus with eccentric nucleoli

Increased risk of recurrence and distant metastases

Papillary type:

Relatively uniform meningoendothelial cells in perivascular pseudopapillary pattern, resembling perivascular pseudorosettes of ependymoma

Aggressive behaviour and propensity to recur and metastasize

Children and young adults

Metastases

Extremely uncommon for meningiomas to metastasize

If occurs; generally associated with anaplastic or malignant patterns

Common sites: lungs, lymph nodes, liver, bones, and heart

Histologically benign meningiomas may also metastasize

Decision Making

Treatment depends on:

Natural growth rateRadiological characteristicsLocationClinical StatusAssessment balancing morbidity of conservative vs invasive technique

Dr. Takeshi Kawase et. Al 2006 rules for treating cranial base meningiomas

Score to each tumor based on predetermined risk characteristics

Attachment/size (0-2)Arterial involvement (0-2)Relation to brainstem (0-2)Cranial nerve involvement (0-2)

Higher score = lower chance of complete resection

Dr. Joung Lee, Cleveland Clinic

“CLASS” algorithm for treatmentCompares negative features (comorbidity, location and age) against benefits (size and symptoms) and assigns a scoreComorbidity (-2-0)Location (-2-0)Age (-2-0)Size (0-2)Symptoms and signs (0-2)

Negative features are related to increased chance of having an undesirable postoperative outcome

Conservative Treatment

2/3rd of asymptomatic – do not continue to grow and may be observed

Absolute growth rate vary between 0.03 and 2.62 cm3 per year.

Annual growth rates calculated as the difference in tumor volume between the initial and latest imaging, divided by the time interval (years) between these determinations

Tumor growth defined as an annual increase in tumor volume more than 1 cm3 per year

Nakamura et al, studied 41 patients with asymptomatic meningiomas

Majority 66% of growth rates less than 1 cm3 per year

Some authors recommend the surgical resection of meningiomas when the tumor growth rate is greater than 1 cm3 per year

Radiological features like partial or complete calcification is related to slow growth rate or absence of growth

Asymptomatic meningiomas with displacement and compression of delicate structures: spinal cord, optic nerve, chiasm, and brainstem or with considerable surrounding edema should be considered for early treatment

Follow up MRI: first at 3 months, second at 6 months and then every year for asymptomatic or MINIMALLY SYMPTOMATIC elderly with fewer than 10-15 years of remaining life expectancy

Surgical Treatment

General Surgical PlanningPreoperative Embolization

Goal: to decrease intraoperative blood loss

Superselective catheterization makes the procedure safer

Proximal occlusion reduces blood supply temporarily and collateral flow develops quickly

Possibility of necrosis induced by vascular occlusion and softening of tumor should be compared to increase of collateral supply

Optimal interval could be between 3 and 9 days

Complications:Painful trismusFacial painScalp necrosisIschemic strokeIntratumoral hemorrhage

Neuronavigation

Principle based on 3D volumetric information obtained from preoperative CT, angiographic CT and MRI images

Possibility of brain shift during tumor debulking may make preop MRI less accurate

This can be solved by intraoperative MRI

Brain shift has minimal impact in meningioma surgery because it is adherent to more rigid structures like skull bone.

General Microsurgical Technique

Dural origin of the tumor primarily coagulated using bipolar reduces tumor vascularization

Internal debulking using suction or CUSA

Cleavage plane between tumor capsule and the underlying arachnoidal sheet identified and preserved using cottonoid

Thinned tumor capsule pulled toward the center of decompression

Only confirmed feeding arteries coagulated and divided

In large tumors, portions of completely dissected and devascularized capsule removed to provide better visualization of deeper structures

Sequential steps of internal decompression, extracapsular dissection and removal of dissected devascularized capsule repeated until the meningioma is totally removed.

All affected dura and bone surrounding the tumor removed, preserving adjacent neurovascular structures

When total resection implies significant risk of morbidity, subtotal removal considered with observation and reoperation /RT for tumor growth and new symptoms

General Recurrence Rate:

1957, Simpson

Grd I: complete tumor removal with resection of dura and bone

Grd II: complete tumor removal with coagulation of dural attachment

Grd III: complete tumor removal without resection or coagulation of dural attachments

Grd IV: subtotal removal

Grd V: decompression

Grd I through IV had recurrence rates of 9%, 19%, 29% and 40%, respectively, at a follow up period of 10 years

Radiation Therapy:

Fractionated Radiotherapy

Effective in primary, unresectable, aggressive, residual, and recurrent meningiomas

Patients with poor clinical status

50-55 Gy – improvement of symptom and tumor control up to 80-86% at 5 years

In aggressive meningiomas (WHO II and III), radiation even with GTR to reduce high recurrence risk

Progression free survival with subtotal resection is increased to 89% with RT vs just 43% with simple observation only

Worsening of neurological symptoms, radionecrosis, memory and cognitive deficit and chronic otitis complication reduced with newer modalities

Stereotactic Radiosurgery

Single high dose of precisely targeted radiation

Eg. Gamma knife, linear accelerator, proton beam, cyberknife, robotic radiosurgery

15 Gy is as equally effective as conventional higher dose

Meningiomas of <3 cm associated with better local control

Fractionated stereotactic conformal radiotherapy

Adv: possibility of delivering higher doses but maintaining stereotactic accuracy

Doses: 50-54 Gy

Intensity Modulated Photon

IMRT – advanced form

Delivers conformal isodose of photon beams to a selected area

Proton beam Therapy:

PBT delivers protons instead of photons

More conformal and homogenous

Decreases the dose in surrounding tissue compared to photon

Treatment result similar to IMRT

Chemotherapy

Generally ineffective

Cytotoxic drugs, immunomodulation, molecular agents, hormonal therapy no significant success.

Cyclophosphamide, adriamycin and vincristine combination modest activity against malignant meningiomas and may improve median survival time.

Interferon alpha 2 b – some success in preventing meningioma growth

Hydroxyurea – arrests meningioma cell growth in S phase of cell cycle induces apoptosis.

Hemangiopericytoma

Arises from meninges but uncertain cell of origin

Similar clinical features and radiological appearance

Angiography shows more prominent vascular supply

Tends to invade adjacent bone and recur even after apparent complete surgical removal

Post op radiotherapy delays recurrence

Thank you!!!

Parasagittal Meningiomas

16.8% of all meningiomas

Classified based on their location along SSS + invasion

Anterior third: from crista galli to coronal sutureMiddle third: from coronal to lamboid suturePosterior third: from lamboid suture to trocula

Sindou classification

Type I: attachment to the outer surface of the sinus wall

Type II: Fragment inside the lateral recess

Type III: Invasion of the ipsilateral wall

Type IV: Invasion of the lateral wall and roof

Type V and VI: complete sinus occlusion, with or without one wall free respectively

For Simpson Grade I and II radical resection: infiltrated SSS should be removed with the tumor

Clinical Features

Lying near vertex: affect ‘foot’ and ‘leg’ area of the motor or sensory strip

Partial seizures or pyramidal weakness may develop in the leg (primarily affecting foot dorsiflexion and knee/hip flexion)

Bilateral weakness if extension of lesion through the falx

Tumors arising anteriorly: extensive growth before focal signs minor impairment of memory, intellect and personality progresses to profound dementia

Posterior third tumor: homonymous hemianopia

Anterior and posterior tumors more silent growth

Evaluation

MRV – not adequate to judge sinus patency

Angiography – best study for surgical planning

Best test of patency may only be at surgery with tentative entry to sinus

Arterial phase – predict difficulty of dissection between the capsule and cortex when pial vascular supply identified

Late venous phase – for evaluating sinus infiltration and presence of collateral veins

Angiography – also allows embolization in vascular meningiomas

Navigation – for locating tumor

Pathology:

WHO grade I – 79.6%WHO grade II – 14.8%WHO grade III – 3.7%

Treatment

Observation – asymptomatic elderly and tumor < 3cm

SSS total or partial invasion: radical resection of sinus with or without venous reconstruction

Risks of SSS resection:intraoperative or postoperative hemorrhagesinus occlusioncorticovenous thrombosisvenous infarction leading to brain edema

Residual tumor – followed up and treated with radiosurgery at recurrence

Less aggressive approach:resection of tumor up to the sinus wall leaving the

sinus intact

Surgical Technique

Positioning: supine for anterior and middle third; prone for posterior thirdHead hung so that the tumor side is down

Approach:Neuronavigation guided skin and bone flap marking2 steps craniotomy: elevating a bone flap on the tumor side 1 cm away from the SSSSeparating the dura from the overlying SSSElevating second flap on the contralateral side across the midline

Hemostasis of superior wall of SSS and major dural vessels – oxycellulose packing or bipolar coagulationEpidural bleeding: hitching sutures

Microsurgical resection:Durotomy taking care not to compromise the afferent veins to SSSTumor dissection preserving arachnoid planeAny tumor on SSS wall removed and wall cauterizedSSS wall not opened or reconstructed

Operative results

Black and coworkersanterior third involvement 12.8%middle third 69.2%posterior third 17.9%

Total resection (Simpson grade I and II) in 63.2%

Recurrence free survival rate: 94.7% at 5 years

Falx Meningiomas

Arise from falx cerebri and compress the medial surface of hemisphere

Types: anterior, middle or posterior

Yasargil: Outer falx meningiomas – arising from the body vsInner falx meningiomas – arises adjacent to the

inferior SS (ISS)

8.5% of all intracranial meningiomas

Evaluation

60% - dural tail sign

MRVA – displacement or involvement of ACA; venous phase for SSS and ISS

Pathology:

Transitional pattern - most common

Rx: Observation with radiological follow up for asymptomatic and small lesions

Subtotal resection – if involvement of ACA; RT/SRS for residual

Approach..

Positioning – same as in parasagittal

Bicoronal craniotomy under neuronavigation; bone flap 2.5 cm off the midline on either side

Dura opened towards non dominant side or towards the side of the larger tumor component

Medial aspect of hemisphere retracted to visualize SSS; afferent veins to SSS preserved

Falx divided 1 cm away from the tumor limits to disrupt the blood supply

Steps contd..

Internal debulking to facilitate capsule mobilization

Tumor dissected off the brain parenchyma following the extra-arachnoidal plane

Caution: ACA and its branches

Result: Chung et. Al. 85.2% total resection and 92.6% good outcome

Complications..

Unilateral dural opening to avoid bilateral infarction of bridging veins

Subtotal resection if major arteries encased

Extreme bilateral edema – bone flap should not be repositioned

Thank you!!!